POS0036 CORRELATION BETWEEN SYSTEMIC AND LOCAL EXPRESSION LEVELS OF MIR-146а, MIR-155 AND MIR-223 AND THE ONGOING TREATMENT IN RHEUMATOID ARTHRITIS PATIENTS
Authors: R. Shumnalieva, D. Kachakova, R. Kaneva, Z. Kolarov, S. Monov
Journal: Annals of the Rheumatic Diseases (2022)

Background MicroRNAs (miRNAs) comprise a class of small, non-coding RNAs that serve as important negative regulators of gene expression at posttranscriptional level. Studies have shown remarkable changes in miRNA expression in autoimmune diseases, such as rheumatoid arthritis (RA) which makes them a potential systemic as well as local biomarkers for disease activity (1-3). On the other hand, regulation of miRNA on transcriptional and posttranscriptional level, as well as the effects of endogenous and exogenous factors on miRNA expression is under investigation. Of importance is the possible effect of the ongoing treatment on miRNA expression in the clinical practice. Objectives To analyze the expression levels of miR-146a, miR-155 and miR-223 in peripheral blood (PB) and synovial fluid (SF) from RA patients in regard to the ongoing treatment regimen. Methods A total number of 63 RA patients according to the 1987 ACR criteria were included in the study. Expression levels of miR-146a, miR-155 and miR-223 in 63 PB samples and matched 48 SF samples were determined by qPCR (SybrGreen technology) and compared to healthy controls (HCs). Relative changes of gene expression levels of the studied miRNAs were calculated by 2 -ΔΔCt method. 45 of the studied patients were on systemic treatment, which included non-steroidal antiinflammatory drugs (NSAIDs), glucocorticosteroids (GCS), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and original biological DMARDs. There were no patients treated with conventional target DMARDs or biosimilar DMARDs. SPSS was used for statistical analysis. Results RA PB showed statistically significant overexpression of miR-223 (58.73%) when compared to HCs and only miR-223 expression levels could be used to differentiate RA patients from HCs (p=0.008). RA SF showed overexpression of miR-146a (in 70.83%, p=0.007), miR-155 (in 79.17%, p=1.63x10 -4 ) and of miR-223 (in 79.17%, p=1.64x10 -3 ) when compared to HCs and the studied miRNAs could be used to differentiate RA patients from HCs (p=4.8x10 -4 , р=8.0х10 -5 and р=2.8х10 -4 , respectively). When we analyzed the correlation between the expression of miRNAs and the ongoing treatment we found a statistically significant correlation between the PB expression levels of miR-223 and the use of NSAIDs and GCS (р=0.015 and р=0.04, respectively) and the SF expression levels of miR-146a and miR-155 and the use of NSAIDs (р=0.011 and 7.98х10 -4 , respectively) and GCS (р=0.039 and р=0.009, respectively). The use of csDMARDs and bDMARDs didn’t show correlation with the PB nor the SF expression of the studied miRNAs. Conclusion The correlation between the systemic miR-223 and the local miR-146a and miR-155 expression with the NSAIDs and GCS treatment could be due to the effect of these treatment compounds on the cells lines from which the studied miRNAs origin. In our study there was no correlation between miRNA expression and the use of biological and conventional DMARDs. Further analysis with larger sets including pre- and posttreatment samples is needed to confirm if altered miRNA expression could be influenced by the treatment regimen as well as if miRNAs could serve as biomarkers for treatment response in the clinical practice. References [1]Filková M, Aradi B, Šenolt L et al. Association of circulating miR-223 and miR-16 with disease activity in patients with early rheumatoid arthritis. Annals of the Rheumatic Diseases 2014;73:1898-1904. [2]Filkova M, Ospelt C, Vettori S et al. Circulating Mir-223 Is Associated with Disease Activity and May Predict the Response to Therapy in Treatment naive Patients with Early Rheumatoid Arthritis, Arthritis Rheum., 2012; 64 Suppl. 10: 2123. [3]Kriegsmann M, Randau TM, Gravius S et al. Expression of miR-146a, miR-155, and miR-223 in formalin-fixed paraffin-embedded synovial tissues of patients with rheumatoid arthritis and osteoarthritis. Virchows Arch 469, 93–100 (2016). Acknowledgements The study was supported by Grant 14-D/2012 and Grant 60/2013 funded by Medical University-Sofia. Disclosure of Interests Russka Shumnalieva: None declared, Darina Kachakova: None declared, Radka Kaneva: None declared, Zlatimir Kolarov Speakers bureau: Abbvie, Pfizer, MSD, UCB, Amgen, Simeon Monov Speakers bureau: Abbvie, Pfizer, MSD, UCB, Amgen